Hydrazine → Oxadiazole

HRID 1746142

반응식

HRID 1746142 반응식
COC(=O)[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6](F)[CH:5]=1.Br[C:14]1[CH:18]=[CH:17][O:16][N:15]=1.[NH2:19][NH2:20].C([C:23](CC)(CC)[C:24]([O-:27])([O-])[O-])C>CO.O.C(OCC)(=O)C>[O:10]([C:14]1[CH2:18][CH2:17][O:16][N:15]=1)[C:8]1[CH:9]=[CH:4][CH:5]=[CH:6][CH:7]=1.[O:27]1[CH:24]=[CH:23][N:20]=[N:19]1

참가 물질

9

반응물 4

HCID 9321HydrazineHCID 139338913-Bromo-1,2-oxazoleHCID 21875354TriethylorthoaceateHCID 46311142Methyl 3-fluoro-5-hydroxybenzoate

생성물 2

HCID 10197612OxadiazoleHCID 149604673-Phenoxy-4,5-dihydroisoxazole

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

3-(phenoxy)-4,5-dihydroisoxazole I-224a and I-224b were prepared in 3 steps according to the following procedures: 3-fluoro-5-hydroxybenzoic acid methyl ester is reacted with racemic bromoisoxazole I-14 using Method 5. The resulting methyl ester (1.0 equiv) is dissolved in methanol (0.08 M) after which hydrazine (50 equiv, 50% by weight in water) is added and the reaction is allowed to stir for 14 h. The reaction mixture is then concentrated under vacuum and used directly in the next step. Triethylorthoacetate (8.0 equiv) is added and the reaction is sealed and heated to reflux for 14 h. The reaction is then transferred to a separatory funnel with excess ethyl acetate and water. The organic layer was washed water and brine, drive over sodium sulfate and concentrated under vacuum to provide crude material which was purified using flash silica gel chromatography (gradient ethyl acetate/hexanes) to provide the desired racemic oxadiazole I-224. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=424.5 m/z. Activity: A

후처리

  1. additionis added
  2. concentrationThe reaction mixture is then concentrated under vacuum
  3. customthe reaction is sealed
  4. temperatureheated
  5. temperatureto reflux for 14 h
  6. washThe organic layer was washed water and brine, drive over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customto provide crude material which
  9. customwas purified

출처 및 근거

ORD 기록
ord-f7273679920a4fa4902cc15ea65bfa4c
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09149465B2

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